Despite recent advances in treating ischemic injuries, myocardial infarction is still the leading cause of death for both, women and men. In the United States alone, each year more than 920,000 myocardial infarctions occur of which about 38% result in death. However, many of those who survive a myocardial infarction will be disabled by some loss in cardiac function. The overall economic cost of cardiovascular disease, which includes coronary heart disease, hypertensive disease, heart failure and stroke, are more than twice the amount of cancer in the U.S. and reached an estimated $448.5 billion in 2008.
Vascular perfusion is a key aspect of cardiac function and patients with myocardial ischemia often benefit from restoration of blood flow to occluded vessels by percutaneous coronary intervention (PCI) or thrombolytics (e.g., tissue plasminogen activator (TPA)). Notably, however, re-canalized macroscopic vessels do not always lead to improved microvascular perfusion. This phenomenon is described as “no re-flow” or “low re-flow”. Importantly, the extent of no re-flow is a major determinant of infarct expansion after myocardial infarction. No re-flow may result from destruction of microscopic vessels, which in the present study was termed “vascular rhexis” or other factors such as microemboli, inflammation, release of toxic cellular metabolites, or oxidative stress that cause endothelial cell dysfunction and induce microvascular leaks. Historically, many studies have attempted to reduce infarct size and improve cardiac function through replacement of damaged myocytes and vascular cells by stem/progenitor cell transplantation. Few studies, however, have focused on protection of microvascular endothelial cells at the time of reperfusion to reduce vascular leak and infarct expansion after myocardial infarction. Accordingly, improved methods of treating ischemic reperfusion injury are urgently required.